Noteworthy Chemistry

November 12, 2012

Gold–thiolate complex nanoaggregates luminesce efficiently. Gold–thiolate nanoclusters are commonly prepared by reactions of Au(I)−thiolate complexes with strong reducing agents. These nanoclusters are luminescent in the blue to near-IR region, but their quantum yields rarely exceed 0.1%.

J. Xie and coauthors at the National University of Singapore and Rice University (Houston) developed a set of unique luminogens that are based on gold–thiolate oligomers. The oligomers are nonluminescent in solution, but they become highly emissive when densely aggregated (aggregation-induced emission or AIE).

The authors synthesized the luminescent gold−thiolate nanoclusters with a simple one-pot procedure. They used glutathione, a common thiolate ligand, as the reducing and protecting agent. The nanoclusters’ Au(0)@Au(I)−thiolate core−shell structure was formed by the controlled aggregation of Au(I)−thiolate complexes on in situ–generated Au(0) cores.

The high quantum yields (≈15%), large Stokes shifts (>200 nm), ultrafine size, low toxicity, and good biocompatibility of the gold−thiolate nanoclusters make them promising candidates for luminescence probes in biological settings. (J. Am. Chem. Soc. 2012, 134, 16662−16670; Ben Zhong Tang)

Interfacial effects reveal new insights into autonomous repair. H. Zhang, H. Xia*, and Y. Zhao* at the University of Sherbrooke (QU) and Sichuan University (Chengdu, China) developed self-healing hydrogels from physically cross-linked poly(vinyl alcohol) (PVA) prepared with a freeze–thaw cycling method. Interfacial contact between two cut pieces of PVA hydrogel for 12 h at room temperature led to autonomous repair of the fracture surface and resistance to mechanical deformation.

Increasing the healing time enhanced the restoration level of the fracture stress. For example, the tensile strength increased from 40% with 1 h of healing to 72% after 48 h of healing, compared with the original hydrogel fracture stress. The PVA hydrogels self-healed over at least 10 cycles.

The keys to the healing phenomena are the proximity of the PVA pieces and PVA’s ability to diffuse across the damaged interface. The authors note that these aspects of the process for a given PVA molecular weight are influenced by the PVA concentration (the network architecture), the separation time of the damaged surfaces (i.e., the time for surface rearrangement), and the number of freeze–thaw cycles (crystallinity). (ACS Macro Lett. 2012, 1, 1233–1236; LaShanda Korley)

Green organocatalysts turn cellulose into a “platform” chemical. Biomass-based resources are promising alternatives to fossil fuels. The furan derivative 5-(hydroxymethyl)furfural (HMF, 1) is a “platform” compound derived from biomass, so called because it can be transformed into efficient fuels and useful chemicals.

Cellulose degradation to HMF is conventionally catalyzed by inefficient solid acids or toxic heavy metals. B. R. Caes, M. J. Palte, and R. T. Raines* at the University of Wisconsin—Madison used efficient, recyclable phenylboronic acid catalysts to convert cellulose and cellulose waste to HMF in satisfactory yields.

The authors began their search for a new catalyst by screening a variety of metal chlorides. They chose MgCl2 because of its catalytic activity and abundance in nature. They then enhanced the conversion reaction by adding o-carboxyl–substituted phenylboronic acids, which drive the equilibrium from glucose toward fructose without inhibiting cellulose hydrolysis and monomeric-sugar dehydration.

For example, cellulose can be converted to HMF in 41% yield in the presence of 0.88 wt% H2SO4, 3 equiv MgCl2·6H2O, and 1.2 equiv o-methoxycarbonylphenylboronic acid (2) at 105 °C within 1 h. The ionic liquid 1-ethyl-3-methylimidazolium chloride ([EMIM]Cl) is the solvent. The same protocol was applied to cellulose-containing municipal waste, such as cotton, paper towels, and newspaper.

Rapid conversion requires high boronate loading, but the boronate can be recycled. The authors showed that the recovered boronate retains its catalytic activity through four reaction cycles. Isotopic labeling studies identified an enediol intermediate during the aldose–ketose transformation. (Chem. Sci. 2012, 3, Advance Article DOI: 10.1039/C2SC21403B; Xin Su)

Synthesize a pyridazinone from diphenylacetone. S. Yoshida and co-workers at Astellas Pharma (Ibaraki, Osaka, and Tokyo, Japan), developed a two-step procedure to convert 1,1-diphenylacetone to 6-(diphenylmethyl)pyridazinone, a strong anti-inflammatory agent. They began with an aldol reaction between 1,1-diphenylacetone and ethyl glyoxylate, then treated the coupled product with NH2NH2·H2O.

After optimizing the aldol reaction, the authors attempted to use an aqueous workup, but this generated a double aldol product via addition to the methine 2’-position. In addition, during the quench step, the aldol hydroxy group was eliminated. To circumvent these problems, they developed a one-pot process in which NH2NH2·H2O is added to the aldol reaction mixture before the quench. NH2NH2 addition and cyclization reactions occur as expected, but the final dehydration to the pyridazinone is not complete at –10 °C. Heating to 40 °C accelerates the dehydration, but the yield is only 60%.

The authors observed that the aqueous layer contained some hydrazone that forms by reaction of excess NH2NH2 with the pyridazinone carbonyl group. Fortunately, the hydrazone can be hydrolyzed by heating the aqueous layer to 70 °C and extracting with toluene to give an overall yield of 76%. (Org. Process Res Dev. 2012, 9, 1544–1551; Will Watson)

This compound inhibits human respiratory syncytial virus. Human respiratory syncytial virus (hRSV) is the most common cause of bronchiolitis and pneumonia among infants. Treatment options are limited, and potential vaccines are toxic to infants.

W. E. Severson and coauthors at the Southern Research Institute (Birmingham, AL), the University of Kansas (Lawrence), and the University of Louisville (KY) began their search for hRSV inhibitors by screening more than 300,000 compounds from the Molecular Libraries Small Molecule Repository. After testing antiviral activity, cell cytotoxicity, potency, and selectivity, they narrowed the field to 51 compounds. Of these, in vitro assays showed that compound 1 had the best property profile.

The optimization of molecule 1 began with the proline structure between the sulfone and the aniline groups. Only 2, the L–proline–derived S-enantiomer of 1, is more active than the racemic mixture. With 2 as a template, the authors synthesized series of analogues by modifying various parts of the molecule. These optimizations led to compounds 3 and 4, which have similar potencies to 2.

In vitro tests on these three compounds showed that 2 is toxic to cells, but 3 efficiently inhibits early virus infection. Compound 3 is more potent than ribavirin, the currently used drug. The results from 3 are promising, but further optimization is needed before in vivo testing can begin. (J. Med. Chem. 2012, 55, 8582–8587, Chaya Pooput)

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